cerebellar disease

Priya Shanmugarajah Marios Hadjivassiliou

 

15 April 2015

ataxia

the cerebellum

the “little brain” the number of neurons in the cerebellum (100 billion) exceeds the total number in the remaining parts of the brain contains complete motor and sensory representation of the whole body controls the timing and pattern of motor activation during movement dysfunction causes ataxia (Greek for lack of order)

uniqueness of the cerebellum

purkinje cells are the only output element each purkinje cell accommodates 160 000 synapses (largest no. of synapses in the mammalian brain) tendency to discharge at very high frequency rich provision of voltage gated ion channels, particularly calcium channels with an intricate system of control of intracellular calcium concentration

symptoms of cerebellar dysfunction

slurring of speech (staccato speech) swallowing difficulties (choking bouts) oscillopsia (not very common) clumsiness (arms and legs) (action) tremor loss of precision of fine movement / motor skills unsteadiness when walking / worse in the dark stumbles and falls cognitive problems

signs of cerebellar dysfunction

nystagmus (other abnormalities of eye movements) dysarthria action tremor truncal ataxia dysdiadochokinaesia limb ataxia gait ataxia

classification of ataxias

1 congenital ataxias (eg cerebellar dysgenesis)

2  diseases where ataxia is one of many features (usually autosomal recessive diseases)

3  episodic ataxias (eg EA1,2…) 4 autosomal recessive ataxias (eg FA) 5 autosomal dominant ataxias (SCA’s) 6  sporadic ataxias (eg MSA-C, gluten ataxia, toxic effects)

(ataxias due to structural damage are not included)

a clinical approach to the ataxias (1)

history age of onset rate of progression additional features (autonomic - bladder, postural BP) pattern of involvement detailed family history alcohol intake exposure to drugs toxic to the cerebellum

a clinical approach to the ataxias (2)

examination eye involvement (nystagmus, broken pursuit) limb ataxia gait ataxia symmetrical vs unilateral evidence of peripheral neuropathy or sensory neuronopathy (sensory ataxia) evidence of postural blood pressure fall

investigation of ataxias

imaging with MRI will exclude: cerebrovascular damage (posterior circulation stroke affecting the cerebellum or its connections) primary tumours (haemangioblastoma, acoustic neuroma,medulloplastoma) secondary tumours hydrocephalus, Chiari malformations multiple sclerosis (primary progressive) white matter involvement in leukodystrophy cerebellar dysgenesis/malformations

causes of familial ataxia

total number of patients assessed 1000 (sheffield ataxia clinic 1996-2013) familial ataxia 195/1000 (20%) autosomal dominant inheritance 139/195 (71%) autosomal recessive inheritance 56/195 (29%)

genetic characterisation 92/195 (47%) commonest AD ataxia is SCA6 commonest recessive ataxia is FA

causes of sporadic ataxia

sporadic ataxia 805/1000 (81%) idiopathic sporadic 218/805 (27%) gluten ataxia 167/805 (21%) alcohol related 113/805 (14% clinically probable MSA-C 92/805 (11%) genetic diagnosis 85/805 (11%)

paraneoplastic ataxia 19/805 (2%) idiopathic sporadic out of total 218/1000 (22%) total presumed genetic 280/1000 (28%)

diagnostic clues

effect of treatment

conclusions

the cerebellum is an extremely complicated “little brain” primarily concerned with precision and refinement of movement ataxia (loss of order in executing movement) is a sign not a disease and results from cerebellar dysfunction ataxia can result from structural damage to the cerebellum or can be genetic or acquired (slowly progressive) acquired diseases account for the majority of causes of ataxia (69%) with familial/genetic ataxias accounting for the remaining 31% in up to 24% of progressive ataxias no cause can be identified

thank you